Optically active 2-hydroxybutyric esters are compounds useful as a reagent or a starting material for producing pharmaceuticals, pesticides, and industrial products. For example, these esters serve as an important starting material for producing (R)-2-[3-[[N-(benzoxazol-2-yl)-N-3-(4-methoxyphenoxy)propyl]aminomethyl]phenoxy]butyric acid, which is a PPARα-selective activating agent and serves as a useful prophylactic and/or therapeutic agent for hyperlipemia, arteriosclerosis, diabetes, diabetes complications, inflammation, heart diseases, etc., and is represented by the following formula (A):
(Patent Document 1).
These optically active 2-hydroxybutyric esters are commercially available reagents (Aldrich), but are very expensive products. Hitherto, as shown in the following schemes, there have been known several processes for producing an optically active 2-hydroxycarboxylic ester derivative; for example, 1) a process for producing an optically active 2-hydroxybutyric ester through asymmetric reduction of a 2-ketobutyric ester by use of baker's yeast (Non-Patent Document 1); 2) a process for producing an optically active 2-hydroxybutyric ester from L-methionine as a starting material (Non-Patent Documents 2 and 3); 3) a process for producing an optically active 2-hydroxycarboxylic ester derivative through asymmetric reduction of an acrylic derivative (Non-Patent Document 4); 4) a process for producing an optically active 2-hydroxycarboxylic derivative from an aldehyde starting material via an optically active cyanohydrin form (Patent Document 2); and 5) a process for producing a 2-hydroxybutyric ester from a 2,3-epoxybutyric ester as a starting material via regio-selective epoxide-ring-opening reaction (Non-Patent Document 5).

However, according to the process 1), chemical yield and optical purity (S-configuration) of the produced 2-hydroxybutyric ester are 42% and 75%, respectively (by use of free baker's yeast) and 42% and 66%, respectively (by use of immobilized baker's yeast). Thus, the process 1) is not suited for the production of high-optical purity 2-hydroxybutyric ester and is not considered an industrially applicable process. In addition, a 2-ketobutyric ester is chemically unstable (Non-Patent Document 1) and very expensive, which is problematic. The process 1) cannot be applied to production of an optically active 2-hydroxybutyric ester of R-configuration.
According to the process 2), a target optically active 2-hydroxybutyric ester can be produced from inexpensive L-methionine as a starting material. However, three steps are required for the target product, resulting in low overall yield, and a large amount of solvent is required for reaction and post treatment. Thus, the process 2) has problematically poor efficiency in terms of production conditions. In addition, since the process 2) includes a step of forming an unstable diazonium salt, reaction conditions are difficult to control, leading to variation in yield and optical purity of the target product. On a certain production scale, optical purity may drop considerably.
According to the process 3), the double bond of a 2-acyloxyacrylic ester derivative is asymmetrically reduced in the presence of an asymmetric catalyst, followed by solvolysis with an acid, whereby a target compound can be produced in high optical purity. However, the 2-acyloxyacrylic ester derivative serving as a starting material is produced through a complicated step, and the process includes preparation of an expensive asymmetric ligand and performing asymmetric reduction under high hydrogen pressure. Thus, the process 3) is not considered an industrially advantageous process.
According to the process 4), a 2-hydroxycarboxylic derivative is produced through two steps including asymmetric transformation of an aldehyde to a cyanohydrin and subsequent hydrolysis. However, preparation of an asymmetric ligand of the catalyst requires a very complex. Depending on a substituent of a reaction substrate, optical purity and chemical yield of the target compound are prone to vary, which is one disadvantage of the process.
The process 5) includes two steps: regio-selectively opening the epoxy ring of an 2,3-epoxybutyric ester by magnesium iodide and, subsequently, performing deiodation reaction, to thereby produce a 2-hydroxybutyric ester. The process has problems including a drop in regio-selectivity of ring-opening reaction caused by undesired reaction temperature, water present in the reaction system, etc.; and unavoidable use of a tin reagent which is stoichiometrically toxic in the subsequent deiodation reaction. Thus, the process 5) is not considered a useful method.
Under such circumstances, demand has arisen for the development of a new process which realizes production of an optically active 2-hydroxybutyric ester in high yield and high optical purity.    Patent Document 1: WO2005/023777, pamphlet    Patent Document 2: Japanese Unexamined Patent Application Publication No. 2004-533490    Non-Patent Document 1: J. Org. Chem., 1988, 53, 2589-2593    Non-Patent Document 2: J. Org. Chem., 1986, 51, 1713-1719    Non-Patent Document 3: Chirality, 1996, 51, 225-233    Non-Patent Document 4: J. Am. Chem. Soc., 1998, 120, 4345-4353    Non-Patent Document 5: Tetrahedron Lett., 1987, 28, 4435-4436